Age-related transcriptional modules and TF-miRNA-mRNA interactions in neonatal and infant human thymus

The human thymus suffers a transient neonatal involution, recovers and then starts a process of decline between the 1st and 2nd years of life. Age-related morphological changes in thymus were extensively investigated, but the genomic mechanisms underlying this process remain largely unknown. Through...

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Published in:PloS one 2020-04, Vol.15 (4), p.e0227547-e0227547
Main Authors: Bertonha, Fernanda Bernardi, Bando, Silvia Yumi, Ferreira, Leandro Rodrigues, Chaccur, Paulo, Vinhas, Christiana, Zerbini, Maria Claudia Nogueira, Carneiro-Sampaio, Magda Maria, Moreira-Filho, Carlos Alberto
Format: Article
Language:English
Subjects:
Age
Age groups
Antigen presentation
Biology and life sciences
Correlation
Depletion
Gene expression
Genes
Heart surgery
Hubs
Identification
Lymphocytes T
Medicine and Health Sciences
Metabolism
miRNA
Modules
Neonates
Network analysis
Newborn babies
Pediatrics
People and Places
Proteins
Thymus
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Summary:The human thymus suffers a transient neonatal involution, recovers and then starts a process of decline between the 1st and 2nd years of life. Age-related morphological changes in thymus were extensively investigated, but the genomic mechanisms underlying this process remain largely unknown. Through Weighted Gene Co-expression Network Analysis (WGCNA) and TF-miRNA-mRNA integrative analysis we studied the transcriptome of neonate and infant thymic tissues grouped by age: 0-30 days (A); 31days-6 months (B); 7-12 months (C); 13-18 months (D); 19-31months (E). Age-related transcriptional modules, hubs and high gene significance (HGS) genes were identified, as well as TF-miRNA-hub/HGS co-expression correlations. Three transcriptional modules were correlated with A and/or E groups. Hubs were mostly related to cellular/metabolic processes; few were differentially expressed (DE) or related to T-cell development. Inversely, HGS genes in groups A and E were mostly DE. In A (neonate) one third of the hyper-expressed HGS genes were related to T-cell development, against one-twentieth in E, what may correlate with the early neonatal depletion and recovery of thymic T-cell populations. This genomic mechanism is tightly regulated by TF-miRNA-hub/HGS interactions that differentially govern cellular and molecular processes involved in the functioning of the neonate thymus and in the beginning of thymic decline.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0227547